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WO2004045372A2 - Compositions cohesives a base d'os demineralise - Google Patents

Compositions cohesives a base d'os demineralise Download PDF

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Publication number
WO2004045372A2
WO2004045372A2 PCT/US2003/036393 US0336393W WO2004045372A2 WO 2004045372 A2 WO2004045372 A2 WO 2004045372A2 US 0336393 W US0336393 W US 0336393W WO 2004045372 A2 WO2004045372 A2 WO 2004045372A2
Authority
WO
WIPO (PCT)
Prior art keywords
composition
demineralized bone
bone matrix
fibers
dbm
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2003/036393
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English (en)
Other versions
WO2004045372A3 (fr
Inventor
Aron D. Rosenberg
Laurent Gilles De Pelichy
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Etex Corp
Original Assignee
Etex Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Etex Corp filed Critical Etex Corp
Priority to KR1020057008746A priority Critical patent/KR101087897B1/ko
Priority to AU2003290884A priority patent/AU2003290884B2/en
Priority to NZ540143A priority patent/NZ540143A/en
Priority to CA002505737A priority patent/CA2505737A1/fr
Priority to EP03783469A priority patent/EP1567044A4/fr
Priority to JP2004553668A priority patent/JP4628791B2/ja
Publication of WO2004045372A2 publication Critical patent/WO2004045372A2/fr
Publication of WO2004045372A3 publication Critical patent/WO2004045372A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/46—Special tools for implanting artificial joints
    • A61F2/4644—Preparation of bone graft, bone plugs or bone dowels, e.g. grinding or milling bone material
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/3608—Bone, e.g. demineralised bone matrix [DBM], bone powder
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/3616—Blood, e.g. platelet-rich plasma
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00—Use of inorganic substances as compounding ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/46—Special tools for implanting artificial joints
    • A61F2/4644—Preparation of bone graft, bone plugs or bone dowels, e.g. grinding or milling bone material
    • A61F2002/4645—Devices for grinding or milling bone material

Definitions

  • the field of the present invention is bone repair and replacement.
  • invention relates to cohesive, formable, and injectable demineralized bone powder
  • compositions in particular, for use in implantation.
  • Bone grafts are used to correct osseous defects that may be caused by trauma
  • defect filler in the form of a stable, moldable putty to facilitate the placement of
  • the medical specialist will take the putty on a spatula or other instrument and
  • DBM demineralized bone matrix
  • DBM is an osteogenic
  • osteoinductive material most commonly obtained from long bone chips demineralized
  • the acid treatment dissolves inorganic mineral components and
  • DBM bone morphogenic proteins
  • TGFs transforming growth factors
  • DBM is fully resorbable, and bone graft materials containing organic DBM are highly biocompatible because it contains many of the components of natural bone.
  • DBM costs less than many other available organic bone composition additives, such as isolated BMPs.
  • DBM is usually available in a lyophilized or freeze dried and sterile form to provide for extended shelf life.
  • the bone in this form is usually very coarse and dry and is, therefore, not conducive to surgical manipulation.
  • U.S. Patent No. 5,073,373 discloses a deformable, shape-sustaining osteogenic composition, in which DBM particles are dispersed within a liquid polyhydroxy carrier, such as glycerol.
  • a liquid polyhydroxy carrier such as glycerol.
  • the vast majority of the DBM particles possess random, irregular geometries with an average median length to median thickness ratio of from about 1 :1 to about 3:1.
  • the combination of the glycerol's high water solubility and reduced viscosity causes the composition to be "runny" and to flow away from the site almost immediately after placement, thus preventing the proper retention of the composition at the implant site (U.S. Patent No. 6,030,635).
  • Bone particles having a median length to median thickness ratio of at least about 10: 1 have been used in osteogenic compositions (U.S. Patent Nos. 5,314,476, 5,510,396 and 5,507,813). These elongated particles have a median length of from about 2 mm to at least about 400 mm and a median thickness from about 0.05 mm to
  • the DBM fibers are commercially available as a preformed fiber sheet, matrix, or workable putty from Osteotech Corporation (Shrewsbury, NJ) under the trade names Grafton® DBM Putty, Grafton® DBM Flex, and Grafton® DBM Matrix.
  • larger DBM particles may also retard the development of new bone by the patient
  • binders such as carboxymethyl cellulose, or the use of high molecular weight
  • hydrogels or other polymers as carrier vehicles has been reported (U.S. Patent Nos.
  • binders provide cohesiveness to the composition only prior to its implantation
  • these binders are eroded or dissolved from the implant site
  • the implant does not retain its shape in vivo.
  • implantation is desirable so that it is able to resist erosion when used as an implant
  • a demineralized bone matrix (DBM)
  • composition that retains its shape (“cohesiveness") before, during and
  • composition e.g., water, saline or bodily fluids.
  • the shape and mass of the composition is
  • the DBM composition includes DBM
  • fibers having an average fiber length in the range from about 250 ⁇ m to about 2 mm
  • the formable mass retains its cohesiveness when immersed in a liquid.
  • the DBM fibers have an average thickness in the
  • the aspect ratio is greater than about 10, or the
  • aspect ratio is in a range from about 10 to about 50.
  • the DBM fibers have an average width to
  • the DBM composition may optionally contain DBM particles having an
  • the DBM composition may optionally contain an osteoinductive additive to
  • the DBM composition may optionally contain an osteoconductive additive to
  • osteoclasts and osteoblasts promote the transport of cells, e.g. osteoclasts and osteoblasts, within the composition.
  • the DBM composition may optionally contain an additive that modifies the
  • composition's handling characteristics are not required to
  • this additive at least partially coats the DBM fibers.
  • the relative amounts of the DBM fibers and the DBM fibers are the relative amounts of the DBM fibers and the DBM fibers.
  • biocompatible liquid range from 1 : 10 to 10 : 1 , or 1 :4 or 4 : 1 , or about 1:1.
  • the DBM fibers are obtained from cortical
  • the DBM composition is injectable through an
  • the DBM composition includes a dry
  • DBM fibers having an average fiber length in the range from
  • the DBM biocompatible fluid in an amount to provide a coherent formable mass.
  • fibers are present in an amount greater than 40 wt % of said dry component.
  • a collection of DBM fibers is provided, of
  • preformed article comprises DBM
  • fibers having an average fiber length in the range from about 250 ⁇ m to about 2 mm
  • the preformed DBM article has a density in the range of about 0.3 g/cc to about 0.7 g/cc.
  • the preformed DBM article has a compression
  • a method for making a DBM composition is
  • a method for making a DBM fiber is
  • biocompatible liquid are combined to produce a coherent, formable mass; the mass is
  • the preformed article is lyophilized. In one or more embodiments, the preformed article is lyophilized. In one or more
  • the lyophilized preformed article has a density of about 0.3 g/cc.
  • the preformed article is oven dried. In one or more embodiments, the preformed article is oven dried. In one or more embodiments, the preformed article is oven dried.
  • the oven dried preformed article has a density of about 0.7 g/cc.
  • Cohesiveness is used herein to mean the ability of DBM, when mixed with a
  • biocompatible fluid to form a malleable or flowable mass and to maintain its shape
  • DBM fibers of the present invention means the ratio of the longest dimension of the
  • FIG. 1 is a schematic illustration of characteristic bone shaving or plate with
  • FIG. 2 is a schematic illustration of a bone shaving apparatus used in the
  • FIG. 3 is a photomicrograph of cortical bone shavings prior to
  • FIG. 4 is a photomicrograph of cortical bone needles prior to deminerahzation
  • FIG. 5 is a photomicrograph of DBM fibers according to at least some embodiments of the present invention.
  • DBM Demineralized bone matrix
  • the DBM fibers have a median thickness in the range from
  • the DBM fibers have an
  • the DBM fibers have an average width to average thickness
  • Natural bone includes compact, noncancellous bone containing parallel and
  • cortical bone either defatted or undefatted, is shaved into
  • thin ( ⁇ 250 ⁇ m) shavings or plates 100 such that the natural bone lamellae, or osteons
  • osteons are naturally aligned along the bone length such that cortical bone is
  • shavings are derived by turning long bone 220 in a bone lathe 200, which contains a
  • the resultant bone shavings or plates typically have a thickness
  • Exemplary thin bone shavings 300 are shown in the photomicrograph of FIG.
  • one or more embodiments of the present invention may be prepared from cortical,
  • Corticocancellous and cancellous bone because they are less dense and are less dense.
  • the shaving procedure described above may be cut into short fibers using
  • fragments may be defatted prior to deminerahzation.
  • the resultant fibers are of low inorganic content, e.g. typically not more
  • the fibers are combed to reduce entanglement using standard fiber
  • bone needles are formed
  • Bone shavings and plates may be stirred in
  • FIG. 4 high aspect ratio bone needles are shown in FIG. 4.
  • the needle structure promotes the
  • the resultant DBM fibers form fine, rope-like fibers as shown in FIG. 5.
  • fibers are of irregular shape, having linear, serpentine, hooked or curved shapes. Due to
  • the fibers may
  • the resultant composition may be molded or injected into
  • paste is injectable through an 18-gauge needle.
  • paste is injectable through an 18-gauge needle.
  • compositions using DBM fibers having the dimensions of the Grafton® DBM fibers having the dimensions of the Grafton® DBM fibers
  • the liquid may be any biocompatible liquid, including water, saline solution,
  • DBM fibers such as serum, bone marrow aspirant and blood, additionally contain
  • osteoinductive factors that will promote bone growth at the site to which the composition is applied.
  • viscous carrier liquids e.g. glycerol, gel, gelatin, hyaluronic acid, or hydrogel
  • fiber DBM compositions of the present invention may be formed using aqueous
  • compositions are not limited to the use of such aqueous solutions.
  • short fiber DBM of the present invention may be used with any biocompatible liquid.
  • biocompatible liquids include but are not limited to liquid
  • polysaccharide derivatives glucose, sucrose, fructose, dextrose, liquid solutions of
  • fatty acid monoesters liquid solutions of glycerol monolaurate, monoacetin, diacetin,
  • the biocompatible liquid is used in any amount sufficient to provide a
  • the ratio of short fiber DBM to carrier liquid ranges from about 1:19 to 19:1 wt/wt, or about 1:10 to 10:1
  • wt/wt or about 1 :4 to 4: 1 wt/wt, or about 2 : 1 to 1 :2 wt/wt, or about 1 : 1 wt/wt,
  • Additional components may optionally be included in the short fiber DBM
  • the short fiber DBM composition may be any suitable composition.
  • the short fiber DBM composition may be any suitable composition.
  • the particulate DBM may be used as an
  • short fiber DBM results from the processing of bone as
  • Particulate DBM suitable for use with the short fiber DBM has
  • DBM particles can range from 0-75wt%, and more preferably 0-50wt%.
  • an osteoinductive component is included in the shaft
  • short fiber DBM composition to further enhance the osteoinductivity of the paste.
  • the DBM fibers and biocompatible liquid may be mixed with bone marrow
  • BMPs or other growth factors, such as TGF or osteogenic proteins, or protein-rich
  • the biocompatible liquid itself
  • the biocompatible liquid is osteoconductive
  • osteoconductive component may be as much as 90% by weight or 50% by weight or
  • the osteoconductive component is any osteoconductive component.
  • a protein present in small amounts, e.g. less than 5wt% of the paste.
  • DBM fibers are naturally osteoconductive, as cells, e.g. osteoclasts and osteoblasts, can move along the length of the fiber to gain access to the composite
  • the interlocking fiber network provides a continuous pathway for improved
  • the DBM fibers can pack more densely than the long
  • an additional osteoconductive component is
  • the short fiber DBM composition included in the short fiber DBM composition to further promote the transport of cells
  • Exemplary osteoconductive compounds include calcium
  • osteoconductive compounds are added to the
  • composition in an amount ranging from about 20 to about 80 wt %, or about 25 to
  • short fiber DBM is combined with one or more
  • osteoconductive serve as
  • carriers for the osteogenic materials may be used to provide strength and/or
  • Calcium phosphate ceramic compositions such as those
  • hydroxyapatite and/or tricalcium phosphate e.g. WO 01/08714 and WO
  • phosphate compositions such as those including amorphous calcium phosphate or
  • PCA poorly crystalline apatitic calcium phosphate
  • phosphate compositions are capable of remodeling into naturally-occurring bone mineral and, therefore, lack the problems associated with the implantation of
  • an osteogenic additive is provided.
  • nanocrystalline calcium phosphate powder prepared from the high energy
  • phosphates are highly reactive and, upon combination with an appropriate
  • physiologically acceptable fluid are capable of self-setting into an apatitic calcium
  • the short fiber DBM is provided in a calcium phosphate powder.
  • powder may be composed of a single calcium phosphate, e.g. an amorphous calcium
  • Amorphous calcium phosphate has a
  • Angstrom scale is a gel-like material formed by rapid precipitation from a
  • amorphous calcium phosphate has a high solubility, high formation rate
  • Amorphous calcium phosphate has a Ca/P ratio in the range of about 1.1 to
  • the amorphous calcium phosphate has a Ca/P ratio of less than about 1.5. In particular embodiments,
  • the Ca/P ratio is between about 1.35 and about 1.49.
  • calcium phosphate may be modified by the introduction of additional ions into the
  • additional ions include CO 3 2" , Mg 2+ , P 2 O 7 4" , nitrate, nitrite or acetate ions.
  • An additional calcium phosphate source may be included in the
  • amorphous calcium phosphate amorphous calcium phosphate.
  • phosphates include calcium metaphosphate, dicalcium phosphate dihydrate,
  • Exemplary basic calcium phosphates include additional amorphous calcium
  • the second calcium phosphate source is
  • DCPD dicalcium phosphate dihydrate
  • the calcium sources When using two or more calcium phosphate sources, the calcium sources
  • the first and second calcium phosphates are used in
  • phosphate has a Ca/P ratio between about 1.1 and about 1.9.
  • sources should have a Ca/P ratio between about 1.1 and about 1.9. In at least some
  • the Ca/P ratio may range from 1.1 to 1.7 and may be that of the desired
  • the calcium phosphate is
  • composition present in the composition in a significant amount.
  • the calcium phosphate is present in an amount greater than or equal to
  • phosphate is present in an amount greater than or equal to about 40 wt % of the dry component.
  • the calcium phosphate powder forms a self-
  • an additive is included in the DBM composition
  • the additive may be a biocompatible polymer, such as a water-
  • soluble cellulosic e.g. carboxymethyl cellulose
  • a natural polymer such as gelatin
  • the additive may be added to either the dry DBM component or the liquid
  • the additive may be used to at least partially coat the DBM fibers prior to the DBM fibers prior to the additive.
  • suitable for use in the DBM composition include gelatin, carboxymethyl cellulose, hydroxypropyl methylcellulose, methylcellulose, hydroxyethyl cellulose, other
  • cellulose derivatives alginate, hyaluronic acid, sodium salts, polyvinyl pyrrolidones,
  • the amount of short fiber DBM that is incorporated in the composition may be any amount of short fiber DBM that is incorporated in the composition.
  • composition or more than about 40 wt % of the dry component of the
  • composition The balance of the dry component is comprised of the optional
  • the short fiber DBM constitutes
  • the DBM composition of the present invention may be provided in the form
  • the kit may include separate packages of the
  • the separate containers may be brought together for mixing immediately before use.
  • the DBM composition may be prepared well in advance and stored
  • the DBM composition of the present invention is
  • the short fiber DBM may be mixed with optional ingredients or the optional
  • ingredients may be added to the biocompatible liquid followed by addition of the
  • composition is delivered to an implant site using methods
  • the composition is injected
  • the composition is formed into the implant site.
  • the composition is formed into the implant site.
  • the DBM composition may be prepared as a high or
  • the composition may be any optional components, the composition may be any optional components.
  • preformed device is lyophilized or vacuum dried.
  • low density, high porosity preformed devices may be prepared having
  • biocompatible liquid According to this method, high density, high strength
  • preformed devices may be prepared having a density as high as about 0.7g/cc and a
  • Example 1 Formation of Short Fiber Demineralized Bone Matrix.
  • This Example describes the preparation of short fiber DBM.
  • This example describes the preparation of a short fiber DBM composition
  • Grafton® DBM Putty which is supplied as a premixture of Grafton® DBM Fibers in
  • glycerol were mixed according to provided instructions to form a malleable paste.
  • the paste was formed into a ball about 0.5 cm in diameter, and the ball was dropped
  • the short fiber DBM sample was
  • This example describes the preparation of an implant of a short fiber DBM
  • This example describes the preparation of an implant of a short fiber DBM -
  • the paste may optionally contain an additive.
  • ACP amorphous calcium phosphate
  • DCPD dicalcium phosphate dihydrate
  • the nanocrystalline calcium phosphate powder was prepared as follows.
  • the pH of the suspension was 13 ⁇ 0.5, which was
  • DCPD was prepared at room temperature by the rapid
  • nanocrystalline calcium phosphate powder 1 cc saline was added per gram dry
  • This Example describes the preparation of a short fiber DBM preformed
  • a short fiber DBM paste cylinder was prepared as described in Example 3.
  • the paste cylinder was then dried in a vacuum oven for four hours at 35 °C to produce
  • the device had a density of about
  • This Example describes the preparation of particulate DBM.
  • the bones were split, and the marrow was
  • resulting bone powder was sieved to between about 125 ⁇ m and about 850 ⁇ m using
  • the sieved bone powder was demineralized by stirring in 0.50 normal
  • Example 7 Implantation of Short Fiber DBM Compositions.
  • particulate DBM prepared as described in Example 6; and (e) Grafton® DBM Putty.
  • the particulate DBM and Grafton® DBM Putty served as controls.
  • IP intraperitoneal
  • Tissue approximately 0.5 cm margins of skeletal muscle and/or connective tissue.
  • Tissue specimens were bisected transversely at the implant midsection, routinely
  • tissue specimens were additionally decalcified

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Transplantation (AREA)
  • Engineering & Computer Science (AREA)
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  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Dermatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Zoology (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
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  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Hematology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Polymers & Plastics (AREA)
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  • Organic Chemistry (AREA)
  • Materials For Medical Uses (AREA)

Abstract

La présente invention concerne des fibres de matrice à base d'os déminéralisé et une composition de matrice à base d'os déminéralisé. Les fibres de la matrice à base d'os déminéralisé présentent une longueur moyenne de fibre se situant entre environ 250 µm et environ 2 mm, et un rapport de forme supérieur à environ 4. La composition de matrice à base d'os déminéralisé inclut des fibres de la matrice à base d'os déminéralisé et un liquide biocompatible en quantité suffisante pour donner une masse cohérente et formable. Cette masse formable conserve sa force de cohésion lorsqu'elle est plongée dans un liquide. L'invention concerne également des procédés concourant à la fabrication des fibres de la matrice à base d'os déminéralisé et de la composition.
PCT/US2003/036393 2002-11-15 2003-11-14 Compositions cohesives a base d'os demineralise Ceased WO2004045372A2 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
KR1020057008746A KR101087897B1 (ko) 2002-11-15 2003-11-14 응집성 탈염화된 뼈 조성물
AU2003290884A AU2003290884B2 (en) 2002-11-15 2003-11-14 Cohesive demineralized bone compositions
NZ540143A NZ540143A (en) 2002-11-15 2003-11-14 Cohesive demineralized bone compositions
CA002505737A CA2505737A1 (fr) 2002-11-15 2003-11-14 Compositions cohesives a base d'os demineralise
EP03783469A EP1567044A4 (fr) 2002-11-15 2003-11-14 Compositions cohesives a base d'os demineralise
JP2004553668A JP4628791B2 (ja) 2002-11-15 2003-11-14 凝集性脱塩骨組成物

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US10/298,112 2002-11-15
US10/298,112 US7582309B2 (en) 2002-11-15 2002-11-15 Cohesive demineralized bone compositions

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CA2505737A1 (fr) 2004-06-03
WO2004045372A3 (fr) 2004-07-08
EP1567044A2 (fr) 2005-08-31
KR20050075416A (ko) 2005-07-20
AU2003290884A1 (en) 2004-06-15
AU2003290884B2 (en) 2009-06-11
JP4628791B2 (ja) 2011-02-09
JP2006508715A (ja) 2006-03-16
US20040097612A1 (en) 2004-05-20
US7582309B2 (en) 2009-09-01
EP1567044A4 (fr) 2009-12-09
KR101087897B1 (ko) 2011-11-30
NZ540143A (en) 2008-04-30

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